The present invention relates to novel fungicidal compounds having a fluorovinyloxyphenyl moiety, a process for preparing same and a fungicidal composition containing same as an active ingredient.
A number of fungicidal compounds have been in practical use to protect crops from various pathogenic fungi; and they may be classified into several groups having similar structural features. However, the repetitive use of a fungicide over a long period induces the appearance of new fungal strains resistant not only to the particular fungicide but also to related fungicides having common structural features. For this reason, continuous efforts have been undertaken to develop fungicides having new structures.
Such efforts have led to the development of new fungicides, e.g., propenoic ester derived from strobilurin (U.S. Pat. No. 4,994,495; WO 94/19331; and U.S. Pat. No. 5,003,101). However, these propenoic ester derivatives have the problem of limited fungicidal activity.
Accordingly, it is a primary object of the present invention to provide a novel compound having a superior fungicidal activity against a wide spectrum of plant pathogenic fungi.
It is another object of the present invention to provide a process for the preparation of said compound.
It is a further object of the present invention to provide a fungicidal composition containing said compound.
In accordance with one aspect of the present invention, there are provided a novel compound of formula (I) and stereoisomers thereof: 
wherein:
X is CH or N; Y is O or S;
Z is O or NH;
R1 is hydrogen or CF3; and
R2 is hydrogen, a C1-10 alkyl, naphthyl, thiophenyl or phenyl group optionally carrying one or more substituents selected from the group consisting of C1-6 alkyl, halogen-substituted c1-6 alkyl, C1-6 alkoxy, phenoxy, halogen and methylenedioxy radicals.
The structure of the compound of formula (I) of the present invention is characterized by the fluorovinyloxyphenoxy moiety, but depending on whether X is CH or N, it may also be classified as a propenoic acid derivative (Xxe2x95x90CH) or as an iminophenylacetic acid derivative (Xxe2x95x90N).
The compound of the present invention has four stereoisomers resulting from two unsymmetrically substituted double bonds, and according to the terminology defined in the Cahn-Ingold-Prelog system(J. March, Advanced Organic Chemistry, 3rd Ed., Wiley-Interscience), these four stereoisomers may be expressed as (E,E), (E,Z), (Z,E) and (Z,Z) isomers, which are included within the scope of the present invention.
Among the compounds of the present invention, preferred are those wherein Y is O; Z is O; R1 is hydrogen; and R2 is a naphthyl or phenyl group optionally substituted with methyl, methoxy or halogen; and those wherein Y is O; R1 is CF3; and R2 is a phenyl group optionally substituted with methyl, methoxy or halogen.
The compound of the present invention may be prepared by the steps of (a) reacting a compound of formula (II) with 3-hydroxyphenol (Resorcinol) in the presence of a base to obtain a compound of formula (III); and (b) reacting the compound of formula (III) with a compound of formula (IV) in the presence of a base, as shown in Reaction Scheme A: 
wherein, X, Y, Z, R1 and R2 have the same meanings as defined in formula (I) above.
Representative compounds of formula (II) are those of formula (II-a) (Xxe2x95x90CH, Yxe2x95x90O and Zxe2x95x90O), formula (II-b) (Xxe2x95x90N, Yxe2x95x90O, Zxe2x95x90O) and formula (II-c) (Xxe2x95x90CH, Yxe2x95x90S, Zxe2x95x90O): 
A compound of formula (II-a) may be prepared by esterification, formylation, methylation and bromination of o-tolylacetic acid according to a conventional method(Yamada, K. et al., Tetrahedron Lett., 2745(1973); Vyas, G. N. et al., Org. Syn. Coll., 4, 836(1963); and Kalir, A., Org. Syn. Coll., 5, 825(1973)), as shown in Reaction Scheme B: 
A compound of formula (II-b) may be prepared by Grignard reaction, oxalylation, condensation and bromination of o-bromotoluene according to a conventional method (Rambaud, M. et al., Synthesis, 564(1988); Korean Patent No. 88,673; and PCT/KR 95/00020), as shown in Reaction Scheme C: 
A compound of formula (II-c) may be prepared by sulfonylation, nucleophilic substitution and bromination of methyl 3-hydroxy-2-(2xe2x80x2-methyl)phenyl-2-propenoate according to a conventional method (Korean Patent Application No. 95-37559), as shown in Reaction Scheme D: 
wherein, MsO represents a methansulfonyloxy group.
Representative compounds of formula (III) are those of formula (III-a) (Xxe2x95x90CH, Yxe2x95x90O and Zxe2x95x90O), formula (III-b) (Xxe2x95x90N, Yxe2x95x90O, Zxe2x95x90O) and formula (III-c) (Xxe2x95x90CH, Yxe2x95x90S, Zxe2x95x90O): 
A compound of formula (II) is reacted with 3-hydroxyphenol in the presence of a base to produce a compound of formula (III). The compound of formula (II) and 3-hydroxyphenol may be used in equimolar amounts and the base may be used in twice the molar amount. The base may be an inorganic base, e.g., sodium hydride, potassium t-butoxide, sodium carbonate or potassium carbonate; or an organic base, e.g., triethylamine or pyridine. The solvent which may be used in the reaction includes acetone, benzene, toluene, tetrahydrofuran, acetonitrile, dichloromethane or dimethylformamide, and the reaction may be conducted at a temperature ranging from room temperature to 100xc2x0 C. The progress of the reaction is conveniently followed by measuring the disappearance of the compound of formula (II) with thin layer chromatography(TLC).
A compound of formula (IV) is reacted with a compound of formula (III) to produce a compound of formula (I), as in Reaction scheme A.
A compound of formula (IV-a), i.e. a compound of formula (IV) wherein R1 is hydrogen, may be prepared by a Grignard reaction, reduction, halogenation, dehalogenation of a halide of R2 according to a conventional method (Herkes, F. E. et al., J. Org. Chem., 32, 1311(1967); and Nemeth, G. et al., J. fluorine Chem., 76, 91(1996)), as shown in Reaction Scheme E: 
wherein R2 has the same meaning as defined in formula (I) above; and W represents a halogen.
A compound of formula (IV-b), i.e. a compound of formula (IV) wherein R1 is CF3, may be prepared by a Grignard reaction and Wittig reaction of a halide of R2 according to a conventional method (Herkes, F. E. et al., J. Org. Chem., 32, 1311(1967); and Wheatman. G. A. et al., J. Org. Chem., 48, 917(1983)), as shown in Reaction Scheme F: 
wherein R2 and W have the same meanings as above.
The compound of the present invention may be prepared by reacting a compound of formula (III) with a compound of formula (IV) in the presence of a base. The compounds (III) and (IV) may be used in equimolar amounts and the base may be used in one to two equivalent amounts. The base may be an inorganic base, e.g., sodium hydride, potassium t-butoxide, sodium carbonate or potassium carbonate; or an organic base, e.g., triethylamine or pyridine. The solvent which may be used in the reaction is benzene, toluene, tetrahydrofuran, acetonitrile, dichloromethane or dimethylformamide, and the reaction temperature is in the range of room temperature to 100xc2x0 C.
In case a mixture of E and Z isomers of compound of formula (II-a-4), (II-b-3) or (II-c-3) is used in the reaction(Reaction Scheme A), the compound of the present invention is obtained as a mixture of four isomers wherein the (E,E) and (E,Z) isomers predominate with minor amounts of the (Z,E) and (Z,Z) isomers. The structures of the four stereoisomers of the compound of the present invention are illustrated below:
In case R1 is hydrogen 
wherein, X, Y, Z, R1 and R2 have the same meanings as defined in formula (I) above.
In case only the E isomer of the compound of formula (II-a-4), (II-b-3) or (II-c-3) is used, the compound of the present invention is obtained as a mixture of the (E,E) and (E,Z) isomers, as is confirmed by 1H-NMR or 19F-NMR analysis.
According to the 1H-NMR analysis(reference compound, TMS) of the compound of the present invention wherein R1 is hydrogen, a hydrogen of vinyl group of (E,E) isomer is shown as a doublet having a coupling constant of 5 to 6 Hz at 5.5 to 5.8 ppm, while that of (E,Z) isomer is represented as a doublet having a coupling constant of 30 Hz at 5.0 to 5.4 ppm. The ratio of the (E,E) isomer to (E,Z) isomer is about 3.5:1 which may be calculated from integration on the 1H-NMR spectroscopy.
According to the 19F-NMR analysis data of the compound of the present invention wherein R1 is CF3, a fluorine substituent of vinyl group and fluorine of CF3 of (E,Z) isomer are shown as a quartet having a coupling constant of 23.4 Hz at xe2x88x9275.9 ppm and a doublet having a coupling constant of 23.7 Hz at xe2x88x9258.5 ppm, respectively, while those of (E,E) isomer are represented as a quartet having a coupling constant of 12.6 Hz at xe2x88x9275.3 ppm and a doublet having a coupling constant of 12.6 Hz at xe2x88x9258.7 ppm. The ratio of the (E,Z) isomer to (E,E) isomer is about 2:1 which may be calculated from integration on the 19F-NMR spectroscopy.
The compound of the present invention wherein Z is NH(the propenamide derivative or iminophenylacetamide derivative of the present invention) may be prepared by reacting the corresponding propenoic ester derivative or iminophenylacetic acid derivative of the present invention with an excess amount of methylamine in an organic solvent, e.g., alcohol including methanol, acetonitrile, dichloromethane or dimethylformamide.
The compound of the present invention has a broad spectrum of fungicidal activity against various plant pathogenic fungus, e.g. Pyricularia orvzae Carvara KA301 which causes Rice Blast, Rhizoctonia solani AG-1 which causes Rice Sheath Blight, Botrvtis cinerae which causes Cucumber Gray Mold Rot, Phytophthora infestans which causes Tomato Late Blight, Puccinia recondita which causes Wheat Leaf Rust and Erysiphe graminis which causes Barley Powdery Mildew.
Accordingly, the present invention also includes within its scope fungicidal compositions comprising one or more of the compounds of formula (I) or stereoisomer thereof as an the compounds of formula (I) or stereoisomer thereof as an active ingredient, in association with fungicidally acceptable carriers.
The fungicidal compositions of the invention may be formulated in various forms such as an emulsion, aqueous dispersion, powder and granules which may contain conventional additives. The compound of the formula (I) may be used in an amount of 10 to 90% on the basis of the weight of an emulsion or aqueous dispersion, and 0.1 to 10% on the basis of the weight of granules.
Fungicidally acceptable carrier that may be used in the present invention is a liquid carrier, e.g., water, an alcohol(ethanol, ethylene glycol, glycerine), ketone (acetone, methylethylketone), ether(dioxane, tetrahydrofuran, cellosolve), aliphatic hydrocarbon (gasoline, Kerosene), halogenated hydrocarbon (chloroform, carbon tetrachloride), amide (dimethylformamide), ester (ethyl acetate, butyl acetate, fatty glycerine ester) and acetonitrile; and a solid carrier, e.g., mineral particle (Kaoline, clay, bentonite, dolomite, talc, silica, sand) and vegetable powder(shrubs).
The additive that may be used in the fungicidal composition of the present invention includes an emulsifier, adhesive, dispersion agent or permeating agent, e.g., nonionic, anionic or cationic interface active agent (fatty acid sodium salt, polyoxy alkyl ester, alkyl sulfonate ester). Further, an agrochemically active ingredient, e.g., an insecticide, herbicide, plant growth regulator, germicide, and fertilizer, may be added in the composition of the present invention.